質(zhì)量控制概要H

ReviewofQualityControl

質(zhì)量控制概要Wewillcover(內(nèi)容)Terminology術(shù)語CharacteristicsofAnalyticalMethods分析方法特性TypesofQCsamplesandhowtheyrelatetothecharacteristicsQC樣品類型和特性1DefinitionofQuality

質(zhì)量的定義Tomostoftheworld(普遍上)degreeofexcellence(優(yōu)異程度)TotheISOworld(在ISO領(lǐng)域)degreeofagreementbetweencharacteristicsandrequirements特性與要求的吻合程度Moreimportantly(更重要)toourclients?(對客戶)2QualityControlvs.QualityAssurance(質(zhì)量控制與質(zhì)量保證)Qualitycontrolisaseriesofmeasurementsusedtoassessthequalityoftheanalyticaldata質(zhì)量控制是一系列測量,以評價(jià)分析數(shù)據(jù)的質(zhì)量Howwellisthetestfulfilling

requirements?試驗(yàn)滿足要求的程度如何?3QualityControlvs.QualityAssurance(質(zhì)量控制與質(zhì)量保證)Qualityassuranceisamanagementplantoensuretheintegrityofdata(asystem)質(zhì)量保證是一種管理計(jì)劃,以確保數(shù)據(jù)的完整性(一種體系)Providesconfidencethatrequirementswillbefulfilled為要求是否得到滿足提供信心4QualitiesofAnalyticalMethods

分析方法的質(zhì)量Accuracy(準(zhǔn)確度)Precision(精密度)Selectivity(選擇性)Sensitivity(靈敏度)Linearity(線性)Range(范圍)Robustness/Ruggedness(穩(wěn)健性/穩(wěn)度)5Accuracy(準(zhǔn)確度)Degreeofagreementbetweenthe“true”valueandthemeasuredvalue(真值與測量值之間的一致程度)6Accuracy(準(zhǔn)確度)Whatisthe“true”value?(什么是真值)Theoretical(理論值)Consensus(公議值)Accepted/Assigned(可接受/賦值)7Accuracy(準(zhǔn)確度)Expressedas(表示為)theratiobetweentheassayedvalueandthe“true”value(%recovery)分析值與真值間的比(%回收率)thedifferencebetweentheassayandtheacceptedtruevalue(%Error)分析與可接受真值間的差(%誤差)8Precision(精密度)Closenessofagreementbetweenmeasurements(測量間的一致程度)Repeatability(r)–sameconditions,shorttimeinterval(samerun)–shorttermprecision重復(fù)性(r)-相同條件下\短時(shí)間間隔-短期內(nèi)精密度Intermediateprecision–samelabdifferentday,analyst,instrument中間精密度-同一實(shí)驗(yàn)室不同日期,分析人員,儀器Reproducibility(R)–agreementbetweenbatchesorbetweenlabs復(fù)現(xiàn)性?-批間或?qū)嶒?yàn)室間的一致性9Precision(精密度)ExpressedasStandardDeviation,RelativeStandardDeviationorRelativePercentDifference表示為標(biāo)準(zhǔn)偏差、相對標(biāo)準(zhǔn)偏差、相對百分差10Sensitivity（（靈敏敏度度））Degreeofresponsetoachangeinanalyteconcentration––resolution被分分析析物物濃濃度度變變化化的的響響應(yīng)應(yīng)變變化化程程度度-分分辯辯率率Lowestconcentrationthatcanbedistinguishedfrombackgroundnoise––detectionlimit能從從背背景景噪噪音音識(shí)識(shí)別別出出的的最最低低濃濃度度-檢檢測測限限11Sensitivity（（靈敏敏度度））Limitofdetectionvs.Limitofquantification（（檢測測限限與與定定量量限限））Limitofdetection(LOD)isthelevelthatwecansaywhetherananalyteispresentornot檢測測限限是是我我們們判判斷斷被被分分析析物物是是否否存存在在的的含含量量水水平平Limitofquantitation(LOQ)isthelevelthatwecanquantifytheanalytewithaspecifiedaccuracy(20%)定量量限限是是我我們們按按規(guī)規(guī)定定準(zhǔn)準(zhǔn)確確度度（（20%））能能對對被被分分析析物物量量化化的的含含量量水水平平12Selectivity（選擇性）Abilitytodetecttheanalyteinacomplexmatrix檢測復(fù)雜基體體中被析物的的能力Abilitytoexcludenon-analytespeciesfromsignal通過信號(hào)排除除非被分析物物的能力Usuallyinverselyrelatedtosensitivity通常與靈敏度度成反比13Linearity（線性）Abilitytoproducearesponsethatisdirectlyproportionaltotheconcentrationoftheanalyte所產(chǎn)生的反應(yīng)應(yīng)與被分析物物濃度成正比比的能力Onlyholdstruewithinagivenrange只在給定范圍圍內(nèi)是真實(shí)的的14Linearity（（線性）Expressedascorrelationcoefficient(r)orcoefficientofdetermination(r2)表示為相關(guān)系系數(shù)(r)或測定系數(shù)(r2)r2=ssxy2/ssxxssyy15Range（（范圍）Theintervalbetweenthehighestandlowestconcentrationforwhichthemethodhasshowntohavesuitablelevelsofaccuracy,precisionandlinearity.在方法具有適適宜的準(zhǔn)確度度、精密度和和線性的條件件下，最高和和最低濃度范范圍16Robustness（（穩(wěn)健性）Abilityofmethodtobeunaffectedbysmallchangesinmethod(internal)conditions（方法不因條件件的較小變化化（內(nèi)部）而而受影響的能能力）Temperature（溫度）pHCompositionofmobilephase（流動(dòng)相組成））Usefulwhenmethodmovesfromdevelopmenttoproduction（（從方法開發(fā)到到使用很有用用）17Ruggedness（（穩(wěn)度）Abilityofmethodtobeunaffectedbyexternalconditions（方法不受外界界條件影響的的能力）Differentanalysts（不同的分析人人員）Differentlaboratories（不同的實(shí)驗(yàn)室室）Differentreagentlots（不同批的試劑劑）Differentinstruments（不同的儀器））18Ruggedness（（穩(wěn)度）Usefulfortechnologytransfer（（對技術(shù)推廣很很有用）19QualityControlMeasures質(zhì)量控制手段段Calibrationstandards（校準(zhǔn)標(biāo)準(zhǔn)）Blanks（空白）Recoverystudies（回收率研究））Precisionstudies（精密度研究））Sensitivitystudies（靈敏度研究））DetectionLimit（（檢測限）Quantitationlimit（定量限）20Calibration(校準(zhǔn))Directlyaffectsaccuracy(直接影響準(zhǔn)確確度)Preparationofstandards(標(biāo)準(zhǔn)制備)Matrix(基體)Stability(穩(wěn)定性)Signaltype:peakarea,peakheight信號(hào)類型:峰峰面積,峰高高21Calibration(校準(zhǔn))Calibrationcurves(校準(zhǔn)曲線)1storder––straightline(一級(jí)-直線)Quadratic––acceptablebutrequiresmorepoints(二次方程-可可以接受,但但需要更多點(diǎn)點(diǎn))Internalstandards(內(nèi)標(biāo))Refinescalibrationresponse(增強(qiáng)校準(zhǔn)響應(yīng)應(yīng))Addedtosamplesandstandards(加入樣品和標(biāo)標(biāo)準(zhǔn)中)Mustbehaveliketheanalyte(象被分析物一一樣表現(xiàn))Cannotbeinsamples––rareelements,deuteratedcompounds(樣品中沒有-稀有元素,含重氘的化化合物)22Calibration(校準(zhǔn))Calibrationverification(校準(zhǔn)驗(yàn)證)Repeatedcalibrationstandard重復(fù)校準(zhǔn)標(biāo)準(zhǔn)準(zhǔn)Intervalmaybeevery20samples(ICPMS)oronceeveryrun(GC-FID)間隔:20個(gè)個(gè)樣品(ICPMS)每次(GC-FID)23Blanks(空白)Usedtomonitorcontamination(監(jiān)測污染)Reagentblanks(試劑空白)Instrumentblanks(儀器空白)Fieldblanks(場地空白)Tripblanks(路途空白)Procedural/methodblanks(程序/方法空空白)Matrixblanks(基體空白)Others?(其它)24RecoveryStudies（回收率研究））Usedtomonitoraccuracy（監(jiān)測準(zhǔn)確度））Matrixspikes（基體加標(biāo)）Fortifiedblanks（增加加標(biāo)）Surrogates（（替代）ReferenceMaterials（參考物質(zhì)）25MatrixSpikes（基體加標(biāo)）Knownamountofanalyteaddedtosample在樣品中加入入已知量的被被分析物Importantwithcomplexmatrix對復(fù)雜基體很很重要Generallyaddedpriortoextractionprocess（通常在在提取取前加加入））Sometimesdifficulttoknowamounttospikeaheadoftime（有時(shí)很很難提提前知知道加加標(biāo)量量）26FortifiedBlanks（（增強(qiáng)空空白））Analytespikeintoreagentblank在試劑劑空白白中加加入被被分析析物標(biāo)標(biāo)樣Carriedthroughsamplepreparationprocess在樣品品準(zhǔn)備備過程程中加加入27Surrogate（替代））Compoundwithsimilarpropertiestotargetanalyte與被分分析物物具有有相近近特性性的化化合物物Addedtoallsamples(unknownsandQC)butnotstandards在所有有樣品品(未未知的的和QC)中加入入，但但標(biāo)樣樣中不不加Usedtomonitormethodperformanceonasample(matrix)specificbasis應(yīng)基于于特定定樣品品（基基體）），用用于監(jiān)監(jiān)測方方法表表現(xiàn)28ReferenceMaterials參考物物質(zhì)Matrixmatchedmaterialswithknownconcentrationofanalytes（被分析析物已已知濃濃度的的基體體匹配配的物物質(zhì)））Maybeexternalorin-house（外部或或室室內(nèi)））Sources（來源））NIST(US)NRC(Canada)EuropeanUnion（（歐盟））CommercialVendors（（商業(yè)渠渠道））29ReferenceMaterials參考物物質(zhì)Usedprimarilytomonitoraccuracy主要用用于監(jiān)監(jiān)測準(zhǔn)準(zhǔn)確度度Maybeusedforotherquality用于其其它質(zhì)質(zhì)量目目的measures(precision,sensitivity)測量（（精密密度、、靈敏敏度））BestoverallQC?（（最好的的全面面質(zhì)量量控制制？））Expensive（費(fèi)用高高）30PrecisionStudies（精密度度研究究）Duplicates（（重復(fù)））Fieldduplicates（（場地重重復(fù)））Labduplicates（（實(shí)驗(yàn)室室重復(fù)復(fù)）Instrumentduplicates（儀器重重復(fù)））Inter-labsplits（（室內(nèi)分分樣））Usedtoidentifyvarianceindifferentprocesses（（用于識(shí)識(shí)別不不同過過程的的變異異）31SensitivityStudies靈敏度研究究Usuallyperformedinitially,thenperiodicallythereafter通常最開始始要做，以以后定期做做Multiplereplicatesofablankorlow-levelstandard空白或低含含量標(biāo)準(zhǔn)多多次重復(fù)32SensitivityStudies靈敏度研究究DetectionLimit––noquantitation檢測限-非非定量QuantitationLimit–Accuracycriteriaadded定量限–準(zhǔn)確度準(zhǔn)則則33SensitivityStudies靈敏度研究究DetectionLimit––99%certaintythattheconcentrationisgreaterthanzero––thattheanalyteispresentinthesample（檢測限—99%確定定濃度大于于0-樣品品中有被分分析物）Uncertaintyishigh(+/-100%ormore)不確定度度高（+/-100%或更高））QuantitationLimit（（定量限））Lowestconcentrationthatcanbedeterminedwithagivenaccuracy(e.g.20%relativeerror)在一定準(zhǔn)準(zhǔn)確度下下（如20%相相對誤差差）可以以測定出出的最低低濃度34Linearity（（線性）Determinedinitiallyandthenasneeded最開始時(shí)時(shí)測定，，然后需需要時(shí)測測定DynamicLinearRangerelatestodetectorresponse動(dòng)態(tài)線性性范圍與與檢測器器響應(yīng)有有關(guān)Alsoconsiderpreparationlimitations也可以認(rèn)認(rèn)為是準(zhǔn)準(zhǔn)備中的的限制Solubilities（（溶解度））Extractionefficiencies（提取率））Derivitizingreactions（衍生反應(yīng)應(yīng)）35WhatdowerunasQC?為什么要要做質(zhì)量量控制Itdependson:（取決于））Typeofinstrumentation儀器類型型StageofMethodDevelopment方法開發(fā)發(fā)階段Typeofanalysis分析類型型36WhatdowerunasQC?為什么要要做質(zhì)量量控制StageofMethodDevelopment方法開發(fā)發(fā)階段Validation（確認(rèn)）Verification/Qualification（驗(yàn)證/判判斷）Routineanalysis（日常分析析）37WhatdowerunasQC?為什么要要做質(zhì)量量控制TypeofAnalysis（分析類型型）Assay（分析）Impurities（雜質(zhì)）Limits（（限制）Content（含量）Identification（識(shí)別）38QualityDataRequiredatMethodValidation（（方法確認(rèn)認(rèn)所需的的質(zhì)量數(shù)數(shù)據(jù)）DataRequired所需數(shù)據(jù)I.D.名稱ImpurityTesting雜質(zhì)檢測AssayContent分析含量Quant.量Limit限Accuracy準(zhǔn)確度NOYESNOYESPrecision精密度NOYESNOYESSelectivity選擇性YESYESYESYESDetectionlimit檢測限NOMAYBE可能YESNOQuantitationlimit定量限NOYESNOMAYBE可能Linearity線性NOYESNOYESRange范圍NOYESNOYES39QualityDataRequiredinRoutineAnalysis日常分析析所需質(zhì)質(zhì)量數(shù)據(jù)據(jù)DataRequired所需數(shù)據(jù)I.D.名稱ImpurityTesting雜質(zhì)檢測AssayContent分析含量Quant.量Limit限Accuracy準(zhǔn)確度NOYESNOYESPrecision精密度NOYESNOYESSelectivity選擇性NOMAYBE1NOMAYBE1Detectionlimit檢測限NONONONOQuantitationlimit定量限NOMAYBENOMAYBELinearity線性NOYESNOYESRange范圍NONONONO1–mayberequiredwhenworkinginunknownmatrix40ReviewofQualityAssurance質(zhì)量保證證概述Wewillcover（內(nèi)容）DefinitionandDescriptionofQA質(zhì)量保證證的定義義和描述述ToolsinaQASystem（QA體系的工工具）ProficiencyTesting（能力驗(yàn)證證）CertifiedReferenceMaterials（有證標(biāo)準(zhǔn)準(zhǔn)物質(zhì)））ValidatedMethods（經(jīng)過確認(rèn)認(rèn)的方法法）41QualityAssurance（質(zhì)量保證證）QualityAssurance質(zhì)量保證證Plannedactionsdesignedtoprovideconfidencethatqualityrequirementswillbefulfilled為質(zhì)量要要求得到到滿足提提供信心心而設(shè)計(jì)計(jì)的有計(jì)計(jì)劃的活活動(dòng)QualityAssuranceSystem質(zhì)量保證證體系A(chǔ)setofprocessesappliedwithinadefinedstructuretogeneratedesiredoutcomes在規(guī)定的的結(jié)構(gòu)內(nèi)內(nèi)產(chǎn)生預(yù)預(yù)期結(jié)果果所采用用的一組組過程Thegoodmanagementofgoodscience良好的科科學(xué)良好好的管理理42QualitySystemComponents質(zhì)量體系系組成Management管理Plan策劃Performance實(shí)施Do做Assessment評價(jià)Review評審436PillarsofQA/QC

QA/QC的六個(gè)基基礎(chǔ)Management管理Facilities設(shè)施Personnel人員CRM’’s有證標(biāo)準(zhǔn)準(zhǔn)物質(zhì)PT’s能力驗(yàn)證證ValidatedMethods經(jīng)確認(rèn)的的方法44ProficiencyTesting能力驗(yàn)證證Providesexternalassessmentofperformance為表現(xiàn)提供供外部評審審Providesabasisforcorrectiveandpreventiveaction為糾正和預(yù)預(yù)防措施提提供基礎(chǔ)45InformationGained搜集信息Comparisonofperformanceagainstanexternalstandard將表現(xiàn)與外外部標(biāo)準(zhǔn)比比較Comparisonagainstpastperformance與過去的表表現(xiàn)比較Comparisonagainstpeer(competitor)labs與同行（競競爭者比較較）Identificationofunsatisfactoryperformers識(shí)別出不滿滿意的操作作者46TypesofPT能力驗(yàn)證類類型Specificanalyte/matrixcombination特定被分析析物/基體體結(jié)合Mercuryinfish（魚中的汞））Benzeneinair（空氣中的苯苯）Fieldofanalysis（場地分析））MetalsbyICP（ICP測金屬）PesticidesbyGC/MS（GC/MS測殺蟲劑））47Samples樣品Sub-sampledfrombulksupply從批中抽取取樣本Discretesamplesplitanddistributed謹(jǐn)慎分割樣樣品并分發(fā)發(fā)48InterlaboratoryComparisons實(shí)驗(yàn)室間比比對Collaborativestudies協(xié)同研究Certificationstudies認(rèn)證研究Round-robinstudies循環(huán)研究49SelectionofPTprogramsPT方案的選擇擇Availabilityofrelevantprograms是否有相關(guān)關(guān)方案Organizationofrelevantprograms相關(guān)方案的的組織Anyprogramisusuallybetterthannothing只有要方案案，總比沒沒有好50AssessmentofPTPrograms

PT方案的評價(jià)價(jià)Beforecommittinglong-termconsider在實(shí)施前應(yīng)應(yīng)考慮Statisticsusedtointerpretdata解釋結(jié)果的的統(tǒng)計(jì)技術(shù)術(shù)How““true”valueisdetermined真值如何確確定Theoretical理論值Refereelab參考實(shí)驗(yàn)室室Consensus公議值51ScoringofParticipants參加者的評評價(jià)Z–score（Z值）Deviationfrom“true””valuedividedbysigma測得值與真真值之差除除以σSigmamaybeanaccepteddeviationorstatisticallydeterminedineachroundσ可能能是是可可接接受受的的偏偏差差或或每每輪輪測測試試的的統(tǒng)統(tǒng)計(jì)計(jì)結(jié)結(jié)果果52ScoringZ-值GenerallyaZ-score（（Z-值））<2isconsideredsatisfactory（（滿意意））>2,<3isconsideredquestionable（（可疑疑））>3isconsideredunsatisfactory（（離群群））scoresmustbewithin2––sigmaZ-值必必須須在在2-σ之間間53LaboratoryInterpretation實(shí)驗(yàn)驗(yàn)室室的的解解釋釋Viewresultsincontext（（從整整體體上上看看結(jié)結(jié)果果））Dotheyagreewithin-houseQCdata是否否與與室室內(nèi)內(nèi)質(zhì)質(zhì)量量控控制制數(shù)數(shù)據(jù)據(jù)一一致致Trendanalysis(considerhowsigmaisdetermined)趨勢勢分分析析（（考考慮慮σ是如如何何確確定定的的））Performanceofotherparticipants其它它參參加加者者的的表表現(xiàn)現(xiàn)54LaboratoryInterpretation實(shí)驗(yàn)驗(yàn)室室的的解解釋釋Comparemethodologyandre-calculateifpossible比較方法，如如果可能重新新計(jì)算Compareuncertaintyagainstin-houseestimates將不確定度與與室內(nèi)評估比比較55CorrectiveActions糾正措施Determinewhentotakeaction確定何時(shí)采取取措施After1unsatisfactoryscore?一個(gè)不滿意結(jié)結(jié)果Aftermany(3)inoneround?一輪中多個(gè)（（如三個(gè)）不不滿意結(jié)果After2consecutiveunsatisfactoryscores?連續(xù)二個(gè)不滿滿意結(jié)果56CorrectiveActions糾正措施Alwaysinvestigate總要調(diào)查Include包括QCdata質(zhì)量控制數(shù)據(jù)據(jù)Calculations,dilutions,transcriptions計(jì)算、稀釋，，抄寫Trainingstatusofanalyst分析人員培訓(xùn)訓(xùn)狀況Performancerecordsofequipment設(shè)備運(yùn)行記錄錄Recordsofcalibrants,reagentsetc.校準(zhǔn)品、試劑劑的記錄等57CorrectiveActions糾正措施Formulateaction公布措施Executeaction實(shí)施措施Checkifactionwassuccessful檢查措施是否否有效58GeneralConsiderations幾點(diǎn)考考慮MoreemphasisisbeingplacedonPTprogramsbyassessors,regulatorsandclients評審員員、管管理部部門和和客戶戶更多多強(qiáng)調(diào)調(diào)PTUsealltheinformationavailable利用所所有可可得到到的信信息HandlePT’slikeroutinesamples(asmuchaspossible)象常規(guī)規(guī)樣品品一樣樣處理理PT樣品（（盡可可能））59ThirdPartyAssessment第三方方評審審AccreditationBodies認(rèn)可機(jī)機(jī)構(gòu)AssessperformanceagainstlaboratoryscoperatherthanPTprogramcriteria在一定定范圍圍內(nèi)評評審實(shí)實(shí)驗(yàn)室室的表表現(xiàn)，，而不不是PT方案準(zhǔn)準(zhǔn)則Consider““fitforpurpose”考慮適適宜性性60ThirdPartyAssessment第三方方評審審Regulators政府管管理部部門MaybeinvolvedindevelopmentofPTprograms可能參參與PT方案的的開發(fā)發(fā)Mayrequireassistancefromprogramcoordinatortoassessresults可能需需要方方案協(xié)協(xié)調(diào)人人來幫幫助評評審結(jié)結(jié)果61ThirdPartyAssessment第三方方評審審Customers客戶WhenusingPTresultsasaperformancestandardensuretargetisrealistic當(dāng)使用用PT結(jié)果作作為能能力標(biāo)標(biāo)準(zhǔn)時(shí)時(shí)，確確保目目標(biāo)是是現(xiàn)實(shí)實(shí)的Mustinvestigateprogram;notjustresults必須調(diào)調(diào)查方方案，，而不不僅是是結(jié)果果62ReferenceMaterials參考物物質(zhì)5types（5種類型型）Puresubstance（（純物質(zhì)質(zhì)）Standardsolutionsandgasmixtures（標(biāo)準(zhǔn)溶溶液和和氣體體混合合物））MatrixRM’s（基體參參考物物質(zhì)））Physicalproperties（物理特特性））Referenceobjects(artifacts)（參考目目標(biāo)））（參參考品品）63ReferenceMaterials參考物物質(zhì)Maybeusedfor可用于于InternalQC內(nèi)部質(zhì)質(zhì)量控控制Methodvalidation方法確確認(rèn)Calibration校準(zhǔn)Estimatinguncertainty評估不不確定定度Training培訓(xùn)64Classification分類CertifiedReferenceMaterials有證參參考物物質(zhì)Directlytraceable直接溯溯源Eachpropertyhasanuncertaintyassociatedwithit每一特特性有有相應(yīng)應(yīng)不確確定度度Referencematerial參考物物質(zhì)Propertiesarehomogenousandthoroughlycharacterizedtobeusedforcalibrationormethodassessment特性是是均勻勻的，，并完完整定定值，，以用用于校校準(zhǔn)或或方法法評價(jià)價(jià)65Availability可獲得得性Generallypoorthereforeexpensive(不容易易獲得得,費(fèi)費(fèi)用高高)Governmentagencies政府機(jī)機(jī)構(gòu)NIST,NRC,EU-BCRTradea